This is a renewal application for a Multipurpose Arthritis and Musculoskeletal Disease Center (MAMDC). The Center brings together medical and health services research activities in rheumatic diseases at four institutions in the San Diego area: the University of California, San Diego, The Scripps Research Institute, the Salk Institute for Biological Studies, and the LaJolla Institutes for Allergy and Immunology (L.J.I.A.I). The Biomedical Research Component of the MAMDC requests funding for five innovative developmental and feasibility projects related to the fundamental etiopathogenesis of rheumatic disease. P.I., M. Croft, (L.J.I.A.I.) Will determine the importance of CD4 lymphocyte subsets in the development and progression of an animal model of rheumatoid arthritis. P.I., L. Feng, (Scripps) will dissect the role of the chemoattractant proteins IL-8 and MCP-1 in experimental arthritis. P.I., D. Green, (L.J.I.A.I.) will test the novel hypothesis that somatic mutations of p53 can lead to aberrant apoptosis in the rheumatoid synovium P.I., C. Rivier, (Salk) will analyze the relationship between the hypothalamic hormone corticotrophin releasing factor, and the proinflammatory cytokine tumor necrosis factor a, in experimental arthritis. P.I., M.P., Corr (UCSD) will use gene therapy to modulate antigen-specific immune responses, without inducing general immunosuppression. The Education, Epidemiology, and Health Services Research (EEHSR) Component encompasses two proposals that focus on health outcome assessments, and their economic consequences, in patients with rheumatic diseases. EEHSR Project 1 P.I., T, Ganiats, (UCSD) will determine if patients discount health outcomes in arthritis in a manner analogous to financial resources, and will investigate whether or not patients with rheumatic diseases prefer near-term benefits to far-term consequences. The next Project, P.I., R. Kaplan, (UCSD) will use a new self-administered quality of well-being (QWB) scale to measure health outcome in patients with chronic musculoskeletal diseases. The Biomedical and EEHSR components of the MAMDC will be supported by three cores. Administration (H.G. Bluestein, Director) will provide overall direction and evaluation of the MAMDC through an Executive Committee assisted by an Outside Advisory Committee: and it will provide day-to-day management and clinical expertise for all MAMDC projects. The Molecular Biology Core (P.P. Chen, Director) will facilitate the timely utilization of molecular biology techniques by physicians and scientists in the Center, and will direct a shared instrumentation facility. The Biostatistics Core (C.Berry, Director) will provide consultation to Center investigators, and will set up a new genetic epidemiology world-wide web site with a focus on arthritis and musculoskeletal disorders.